Mitochondrial DNA Copy-Number Variation and Pancreatic Cancer Risk in the Prospective EPIC Cohort

Cancer Epidemiol Biomarkers Prev. 2020 Mar;29(3):681-686. doi: 10.1158/1055-9965.EPI-19-0868. Epub 2020 Jan 13.


Background: Mitochondrial DNA (mtDNA) copy number in peripheral blood has been found to be associated with risk of developing several cancers. However, data on pancreatic ductal adenocarcinoma (PDAC) are very limited.

Methods: To further our knowledge on this topic, we measured relative mtDNA copy number by a quantitative real-time PCR assay in peripheral leukocyte samples of 476 PDAC cases and 357 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Results: We observed lower mtDNA copy number with advancing age (P = 6.54 × 10-5) and with a high body mass index (BMI) level (P = 0.004) and no association with sex, smoking behavior, and alcohol consumption. We found an association between increased mtDNA copy number and decreased risk of developing PDAC with an odds ratios (OR) of 0.35 [95% confidence interval (CI), 0.16-0.79; P = 0.01] when comparing the fifth quintile with the first using an unconditional logistic regression and an OR of 0.19 (95% CI, 0.07-0.52; P = 0.001) with a conditional analysis. Analyses stratified by BMI showed an association between high mtDNA copy number and decreased risk in the stratum of normal weight, consistent with the main analyses.

Conclusions: Our results suggest a protective effect of a higher number of mitochondria, measured in peripheral blood leukocytes, on PDAC risk.

Impact: Our findings highlight the importance of understanding the mitochondrial biology in pancreatic cancer.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / isolation & purification
  • Case-Control Studies
  • DNA Copy Number Variations*
  • DNA, Mitochondrial / blood
  • DNA, Mitochondrial / genetics*
  • DNA, Mitochondrial / isolation & purification
  • Europe
  • Female
  • Humans
  • Incidence
  • Leukocytes / cytology
  • Male
  • Middle Aged
  • Mitochondria / genetics
  • Pancreatic Neoplasms / blood
  • Pancreatic Neoplasms / epidemiology*
  • Pancreatic Neoplasms / genetics
  • Prospective Studies
  • Protective Factors
  • Real-Time Polymerase Chain Reaction
  • Risk Assessment / methods
  • Risk Assessment / statistics & numerical data
  • Risk Factors


  • Biomarkers, Tumor
  • DNA, Mitochondrial